Quantitative Trait Locus Mapping

Quantitative traiT locus (QTL) mapping is a statistical tool utilizing the science of quantitative trait loci (QTLs). A QTL is a section of deoxyribonucleic acid (DNA) on a chromosome that holds two or more genes which all play a role in a particular trait. QTL mapping has been used to identify genes involved in skin color, body mass, diabetes, cancer, and more.

DNA is organized in the cell into chromosomes. Humans, for example, have 22 pairs of chromosomes along with the two sex chromosomes, or 46 chromosomes all together. Roughly speaking, the chromosomes are organized into noncoding DNA and coding DNA, which encodes ribonucleic acid (RNA) that is usually translated into proteins. The region of a chromosome which encodes a particular RNA or group of RNAs is called a gene. A hypothesis that is the base of QTL theory is that groups of genes near to each other on a chromosome may have a multigene effect on certain polygenic traits. Using sophisticated mathematics and genetic experiments, investigators can examine these gene regions and their relationships to traits. This is the process for QTL mapping. In other words, scientists look at how often particular genes are expressed together in relation (linkage) to specific traits.

With advanced modern technology, scientists can use QTL mapping as a tool for determining the genes involved in a particular trait. For example, if an animal model such as a mouse exhibited a trait similar to a human polygenic trait, researchers could determine which region of DNA is responsible for the trait. This region could then be sequenced and the genes analyzed. The region is found using analysis which determines the regions of DNA that are more likely than chance to associate with a particular trait.

To narrow down from an animal's entire genome to a DNA region of interest, scientists use the technique of markers. Known single-gene characteristics, such as coat color, that are peppered throughout the genome are used to track DNA regions along the trait of interest. If, for a simplified example, in an inbred (genetically identical) colony of obese mice, more obese mice were black than brown, and the difference were greater than chance alone, scientists could statistically determine that the QTL related to that mouse strain's obesity were near to the black coat gene.

[Page 657]Another use of QTL mapping is determining genetics of food sources which might provide more or less nutrition, or might make a consumer more or less susceptible to overweight or obese status. For example, plants or meat animals might be analyzed via QTL mapping, as might dairy cows for milk production.

Because more than one gene is involved, standard rules of Mendelian genetics do not apply to polygenic traits; rather, they are inherited along a spectrum. In other words, the phenotype (usually the physical appearance) of a trait will vary along a gradient—where it lies in the gradient depends on all the individual genes and their interactions. Most polygenic traits are quantifiable phenotypes, hence the “quantitative trait” in QTL. Locus refers to the characteristic of having a position on the chromosome. An example of a polygenic trait that can be quantified is human body weight. Mendelian law predicts every grown child to have an intermediate weight between the weights of the two grown parents. Thus, two children of the same parents should have the same weight. This would be the case if only one gene controlled weight; however, because multiple genes have an effect on body weight, offspring have weights on a gradient, not necessarily falling between the two parental values.

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